Assays that evaluate the biological effects of small molecules in cell cultures are important in many applications including studying the mechanisms of action of natural products, elucidating signal transduction pathways, and screening small molecule libraries in drug discovery programs.1,2 Yet, it is still difficult to measure many biochemical activities in cell-based assays, and therefore these assays cannot be applied to many targets of interest. Indeed, most assays report on a phenotypic behavior, including cell differentiation,3 cell death,4 and migration5 and in those cases they do not measure the inhibition or activation of specific enzymes. Detection methods based on fluorescent proteins6 have allowed the real-time observation of specific enzyme activities, but it remains challenging to develop these reagents and many biochemical activities have not yet been targeted with these approaches.